Skip to main content
Log in

Choosing Appropriate Antidepressant Therapy in the Elderly

A Risk-Benefit Assessment of Available Agents

  • Review Article
  • Adverse Effects
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

This article discusses the advantages and disadvantages of tricyclic antide-pressants (TCAs), tetracyclic antidepressants (i.e. mianserin), selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), triazolopyridines (i.e. trazodone), phenylpiperazines (i.e. nefazodone), serotonin and noradrenaline (norepinephrine) reuptake inhibitors (i.e. venlafaxine), and aminoketones [i.e. amfebutamone (bupropion)] in the treatment of late-life depression. A limitation of the existing literature is that most data regarding drugs are derived from studies that have involved medically stable outpatients who do not have dementia and who are less than 80 years of age. There is a paucity of data on the use of antidepressants in very elderly individuals, patients who have significant medical comorbity and patients with dementia or other neurological problems.

No one class of antidepressant has been found to be more effective than another in the acute treatment of geriatric major depression. However, given design shortcomings in many of these studies, the possibility of a real difference in efficacy between drugs (especially in the treatment of severe or melancholic depression) cannot be excluded. With respect to adverse effects, drug interactions, and dosage and administration, each class of antidepressant has its benefits and limitations. There is no one ‘first-line’ antidepressant for elderly patients with depression. Selection of an antidepressant should be made on a case by case basis, taking into account each patient’s characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blazer DG. Epidemiology of late-life depression. In: Schneider LS, Reynolds CF, Lebowitz BD, et al., editors. Diagnosis and treatment of depression in late life. Washington, DC: American Psychiatric Press; 1994: 9–19

    Google Scholar 

  2. NTH Consensus Development Panel. Diagnosis and treatment of depression in late life. JAMA 1992; 268: 1018–24

    Article  Google Scholar 

  3. Crome P. Drug compliance in the elderly. In: Wheatley D, editor. Psychopharmacology of old age. Oxford: Oxford University Press; 1982: 55–64

    Google Scholar 

  4. Reynolds CF, Frank E, Kupfer DJ, et al. Treatment outcome in recurrent major depression: a post hoc comparison of elderly (‘young old’) and midlife patients. Am J Psychiatry 1996; 153: 1288–92

    PubMed  Google Scholar 

  5. Gerson SC, Plotkin DA, Jarvik LF. Antidepressant drug studies, 1964–1986: empirical evidence for aging patients. J Clin Psychopharmacol 1988; 8: 311–22

    Article  PubMed  CAS  Google Scholar 

  6. Volz HP, Möller HJ. Antidepressant drug therapy in the elderly: a critical review of the controlled clinical trials conducted since 1980. Pharmacopsychiatry 1994; 27: 93–100

    Article  PubMed  CAS  Google Scholar 

  7. Anstey K, Brodaty H. Antidepressants and the elderly: double-blind trials 1987–1992. Int J Geriatr Psychiatry 1995; 10: 265–79

    Article  Google Scholar 

  8. Menting JEA, Honig A, Verhey FRJ, et al. Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects. Int Clin Psychopharmacol 1996; 11: 165–75

    Article  PubMed  CAS  Google Scholar 

  9. Schneider LS. Pharmacologic considerations in the treatment of late-life depression. Am J Geriatr Psychiatry 1996; 4Suppl. 1: S51–S65

    Google Scholar 

  10. Mittmann N, Herrmann N, Einarson TR, et al. The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis. J Affect Disord 1997; 46: 191–217

    Article  PubMed  CAS  Google Scholar 

  11. Mahapatra SN, Hackett D. A randomized, double-blind, parallel-group comparison of venlafaxine and dothiepin in geriatric patien’ts with major depression. Int J Clin Pract 1997; 51: 209–13

    PubMed  CAS  Google Scholar 

  12. Preskorn S, Burke M. Somatic therapy for major depressive disorder: selection of an antidepressant. J Clin Psychiatry 1992; 53Suppl. 9: 1–14

    Google Scholar 

  13. Danish University Antidepressant Group (DUAG). Citalopram: clinical effect profile in comparison with clomipramine: a controlled multicenter study. Psychopharmacology 1986; 90: 131–8

    Google Scholar 

  14. Danish University Antidepressant Group (DUAG). Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect, than clomipramine in a controlled multicenter study. J Affect Disord 1990; 18: 289–99

    Article  Google Scholar 

  15. Danish University Antidepressant Group (DUAG). Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disord 1993; 28: 105–16

    Article  Google Scholar 

  16. Perry PJ. Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord 1996; 39: 1–6

    Article  PubMed  CAS  Google Scholar 

  17. Roose SP, Glassman AH, Attia E, et al. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry 1994; 151: 1735–9

    PubMed  CAS  Google Scholar 

  18. Georgotas A, McCue RE, Cooper TB, et al. How effective and safe is continuation therapy in elderly depressed patients? Arch Gen Psychiatry 1988; 45: 929–32

    Article  PubMed  CAS  Google Scholar 

  19. Georgotas A, McCue RE, Cooper TB. A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients. Arch Gen Psychiatry 1989; 46: 783–6

    Article  PubMed  CAS  Google Scholar 

  20. Reynolds CF, Frank E, Perel JM, et al. Maintenance therapies for late-life recurrent major depression: research and review circa 1995. Int Psychogeriatr 1995; 7 Suppl.: 27–39

    Article  PubMed  Google Scholar 

  21. Old Age Depression Interest Group. How long should the elderly take antidepressants? A double-blind placebo-controlled study of continuation/prophylaxis therapy with dothiepin. Br J Psychiatry 1993; 162: 175–82

    Article  Google Scholar 

  22. Georgotas A, McCue RE, Hapworth W, et al. Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly. Biol Psychiatry 1986; 21: 1155–66

    Article  PubMed  CAS  Google Scholar 

  23. Miller MD, Pollock BG, Rifai AH, et al. Longitudinal analysis of nortriptyline side effects in elderly depressed patients. J Geriatr Psychiatry Neurol 1991; 4: 226–30

    Article  PubMed  CAS  Google Scholar 

  24. Reynolds CF, Frank E, Perel JM, et al. Nortriptyline side effects during double-blind, randomised, placebo-controlled maintenance therapy in older depressed patients. Am J Geriatr Psychiatry 1995; 3: 170–5

    Article  Google Scholar 

  25. Rosen J, Sweet R, Pollock BG, et al. Nortriptyline in the hospitalized elderly: tolerance and side effect reduction. Psychopharmacol Bull 1993; 29(2): 327–31

    PubMed  CAS  Google Scholar 

  26. Katz IR, Simpson GM, Curlick SM, et al. Pharmacologic treatment of major depression for elderly patients in residential care settings. J Clin Psychiatry 1990; 51Suppl. 7: 41–7

    PubMed  Google Scholar 

  27. Lipsey JR, Robinson RG, Pearlson GD, et al. Nortriptyline treatment of post-stroke depression: a double-blind study. Lancet 1984; I: 297–300

    Article  Google Scholar 

  28. Koenig HG, Breitner JCS. Use of antidepressants in medically ill older patients. Psychosomatics 1990; 31: 22–32

    Article  PubMed  CAS  Google Scholar 

  29. Young RC, Mattis S, Alexopoulos GS, et al. Verbal memory and plasma drug concentrations in elderly depressives treated with nortriptyline. Psychopharmacol Bull 1991; 27(3): 291–4

    PubMed  CAS  Google Scholar 

  30. Meyers BS, Mattis S, Gabriele M, et al. Effects of nortriptyline on memory self-assessment and performance in recovered elderly depressives. Psychopharmacol Bull 1991; 27(3): 295–9

    PubMed  CAS  Google Scholar 

  31. Hoff AL, Shukla S, Helms P, et al. The effects of nortriptyline on cognition in elderly depressed patients. J Clin Psychopharmacol 1990; 10(3): 231–2

    Article  PubMed  CAS  Google Scholar 

  32. Halper JP, Mann JJ. Cardiovascular effects of antidepressant medications. Br J Psychiatry 1988; 153Suppl. 3: 87–98

    CAS  Google Scholar 

  33. Roose SP, Glassman AH, Giardina EGV, et al. Nortriptyline in depressed patients with left ventricular impairment. JAMA 1986; 256: 3253–7

    Article  PubMed  CAS  Google Scholar 

  34. Roose SP, Dalack GW. Treating the depressed patient with cardiovascular problems. J Clin Psychiatry 1992; 53Suppl 9.: 25–31

    PubMed  Google Scholar 

  35. Roose SP, Glassman AH. Antidepressant choice in the patient with cardiac disease: lessons from the cardiac arrhythmia suppression trial (CAST) studies. J Clin Psychiatry 1994; 55 (9 Suppl. A): 83–7

    PubMed  Google Scholar 

  36. Preskorn SH. Recent pharmacologic advances in antidepressant therapy for the elderly. Am J Med 1993; 94(Suppl. 5A): 2–12S

    Google Scholar 

  37. Rockwell E, Lam RW, Zisook S. Antidepressant drug studies in the elderly. Psychiatr Clin North Am 1988; 11: 215–33

    PubMed  CAS  Google Scholar 

  38. Sallee FR, Pollock BG. Clinical pharmacokinetics of imipramine and desipramine. Clin Pharmacokinet 1990; 18: 346–64

    Article  PubMed  CAS  Google Scholar 

  39. von Moltke LL, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of antidepressants in the elderly. Clin Pharmacokinet 1993; 24: 141–60

    Article  Google Scholar 

  40. Rolan PE. Plasma protein binding displacement interactions: why are they still regarded as clinically important? Br J Clin Pharmacol 1994; 37: 125–8

    Article  PubMed  CAS  Google Scholar 

  41. Pollock BG, Perel JM, Paradis CF, et al. Metabolic and physiologic consequences of nortriptyline treatment in the elderly. Psychopharmacol Bull 1994; 30(2): 145–50

    PubMed  CAS  Google Scholar 

  42. Crewe HK, Lennard MS, Tucker GT, et al. The effect of selective serotonin re-uptake inhibitors on cytochrome P450 2D6 (CYP 2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992: 34: 262–5

    Article  PubMed  CAS  Google Scholar 

  43. Wakeling A. Efficacy and side effects of mianserin, atetracyclic antidepressant. Postgrad Med J 1983; 59: 229–31

    Article  PubMed  CAS  Google Scholar 

  44. Kerr JS, Sherwood N, Hindmarch I. The comparative psychopharmacology of 5HT reuptake inhibitors. Hum Psychopharmacol 1991; 6: 313–7

    Article  CAS  Google Scholar 

  45. Macquire KP, Norman TR, Burrows GD, et al. A pharmacokinetic study of mianserin. Eur J Clin Pharmacol 1982; 21: 517–22

    Article  Google Scholar 

  46. Leinonen E, Koponen H, Lepola U. Serum mianserin and ageing. Prog Neuropsychopharmacol, Biol Psychiatry 1994; 18: 833–45

    Article  CAS  Google Scholar 

  47. Shami M, Elliot HL, Kelman AT, et al. The pharmacokinetics of mianserin. Br J Clin Pharmacol 1983; 15: 313S–22S

    Article  PubMed  Google Scholar 

  48. Begg EG, Sharman JR, Kidd JE, et al. Variability in the elimination of mianserin in elderly patients. Br J Clin Pharmacol 1989; 27: 445–51

    Article  PubMed  CAS  Google Scholar 

  49. Sasa H. Steady state plasma kinetics of mianserin and its major metabolite desmethylmianserin. Jpn J Neuropsychopharmacology 1992; 14: 441–8

    CAS  Google Scholar 

  50. Goodnick PJ. Pharmacokinetic optimisation of therapy with newer antidepressants. Clin Pharmacokinet 1994; 27: 307–30

    Article  PubMed  CAS  Google Scholar 

  51. Thomas DR, Nelson DR, Johnson AM. Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology 1987; 93: 193–200

    Article  PubMed  CAS  Google Scholar 

  52. Geretsegger C, Bohmer F, Ludwig M. Paroxetine in the elderly depressed patient: randomised comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol 1994; 9: 25–9

    Article  PubMed  CAS  Google Scholar 

  53. Grimsley SR, Jann MW. Paroxetine, sertraline and fluvoxamine: new selective serotonin reuptake inhibitors. Clin Pharm 1992; 11: 930–57

    PubMed  CAS  Google Scholar 

  54. Sheehan D, Dunbar GC, Fuell DL. The effect of paroxetine on anxiety and agitation associated with depression. Psychopharmacol Bull 1992; 28: 139–43

    PubMed  CAS  Google Scholar 

  55. Tollefson GD, Greist JH, Jefferson JW, et al. Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. J Clin Psychopharmacol 1994; 14: 385–91

    PubMed  CAS  Google Scholar 

  56. Rickeis K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. J Clin Psychiatry 1990; 51 (12 Suppl. B): 9–12

    Google Scholar 

  57. Brown WA, Harrison W. Are patients who are intolerant to one serotonin selective reuptake inhibitor intolerant to another? J Clin Psychiatry 1995; 56: 30–4

    PubMed  CAS  Google Scholar 

  58. Laghrissi-Thode F, Pollock BG, Miller M, et al. Comparative effects of sertraline and nortriptyline on body sway in older depressed patients. Am J Geriatr Psychiatry 1995; 3: 217–28

    Article  Google Scholar 

  59. Liu BA, Mittmann N, Knowles SR, et al. Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports. Can Med Assoc J 1996; 155: 519–27

    CAS  Google Scholar 

  60. Flint AJ, Crosby J, Genik JL. Recurrent hyponatremia associated with fluoxetine and paroxetine [letter]. Am J Psychiatry 1996; 153: 134

    PubMed  CAS  Google Scholar 

  61. Mattila MJ, Saarialho-Kere U, Mattila M. Acute effects of sertraline, amitriptyline, and placebo on the psychomotor performance of healthy subjects over 50 years of age. J Clin Psychiatry 1988; 49(8 Suppl.): 52–8

    PubMed  Google Scholar 

  62. Hindmarch I, Shillingford J, Shillingford C. The effects of sertraline on psychomotor performance in elderly volunteers. J Clin Psychiatry 1990; 51 (12 Suppl. B): 34–6

    PubMed  Google Scholar 

  63. Hindmarsh I, Kerr JS. Effects of paroxetine on cognitive function in depressed patients, volunteers and elderly volunteers. Med Sci Res 1994; 22: 669–70

    Google Scholar 

  64. McEntee W, Oxman T, Ko G, et al. The effects of sertraline on cognition in depressed geriatric patients [abstract]. Psychopharmacol Bull 1996; 32(3): 486

    Google Scholar 

  65. Sheline YI, Freedland KE, Carney RM. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease? Am J Med 1997; 102: 54–9

    Article  PubMed  CAS  Google Scholar 

  66. Roose SP, Laghrissi-Thode F, Kennedy JS, et al. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA 1998; 279: 287–91

    Article  PubMed  CAS  Google Scholar 

  67. Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996; 153: 311–20

    PubMed  CAS  Google Scholar 

  68. Shader RI, von Moltke LL, Schmider J, et al. The clinician and drug interactions: an update. J Clin Psychopharmacol 1996; 16: 197–201

    Article  PubMed  CAS  Google Scholar 

  69. Harvey AT, Preskorn SH. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors: part II. J Clin Psychopharmacol 1996; 16: 345–55

    Article  PubMed  CAS  Google Scholar 

  70. Newhouse PA. Use of serotonin selective reuptake inhibitors in geriatric depression. J Clin Psychiatry 1996; 57Suppl. 5: 12–22

    PubMed  CAS  Google Scholar 

  71. Rifkin A. SSRI optimal dose remains at issue. J Clin Psychiatry 1997; 58: 87–8

    Article  PubMed  CAS  Google Scholar 

  72. De Vane CL. Pharmacokinetics of the selective serotonin reuptake inhibitors. J Clin Psychiatry 1992; 53Suppl. 2: 13–20

    Google Scholar 

  73. Thase ME, Trivedi MH, Rush AJ. MAOIs in the contemporary treatment of depression. Neuropsychopharmacology 1995; 12: 185–219

    Article  PubMed  CAS  Google Scholar 

  74. Mallinger AG, Smith F. Pharmacokinetics of monoamine oxidase inhibitors. Psychopharmacol Bull 1991; 27: 493–502

    PubMed  CAS  Google Scholar 

  75. Gardner DM, Shulman KI, Walker SE, et al. The making of a user friendly MAOI diet. J Clin Psychiatry 1996; 57(3): 99–104

    PubMed  CAS  Google Scholar 

  76. Flint AJ, Rifat SL. The effect of sequential antidepressant treatment on geriatric depression. J Affect Disord 1996; 36: 95–105

    Article  PubMed  CAS  Google Scholar 

  77. Georgotas A, Friedman E, McCarthy M, et al. Resistant geriatric depressions and therapeutic response to monoamine oxidase inhibitors. Biol Psychiatry 1983; 18(2): 195–205

    PubMed  CAS  Google Scholar 

  78. Sunderland T, Cohen RM, Molchan S, et al. High-dose selegiline in treatment-resistant older depressive patients. Arch Gen Psychiatry 1994; 51: 607–15

    Article  PubMed  CAS  Google Scholar 

  79. Nair NPV, Ahmed SK, Ng Ying Kin NMK, et al. Reversible and selective inhibitors of monoamine oxidase A in the treatment of depressed elderly patients. Acta Psychiatr Scand 1995; 91Suppl. 386: 28–35

    Article  Google Scholar 

  80. Moll E, Hetzel W. Moclobemide safety in depressed patients. Acta Psychiatr Scand 1990; 82Suppl. 360: 69–70

    Article  Google Scholar 

  81. Wesnes KA, Simpson PM, Christmas L, et al. The effects of moclobemide on cognition. J Neural Transm 1989; 28 Suppl.: 91–102

    CAS  Google Scholar 

  82. Anand R, Wesnes KA. Cognition-enhancing effects of moclobemide, a reversible MAO-inhibitor, in humans. Adv Neurol 1990; 51: 261–8

    PubMed  CAS  Google Scholar 

  83. Gram LF, Guentert TW, Grange S, et al. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: a panel study. Clin Pharmacol Ther 1995; 57: 670–7

    Article  PubMed  CAS  Google Scholar 

  84. Stoeckel K, Pfefen JP, Mayersohn M, et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. Acta Psychiatr Scand 1990; 82Suppl. 360: 94–7

    Article  Google Scholar 

  85. Nair NPV, Amin M, Holm P, et al. Moclobemide and nortriptyline in elderly depressed patients: a randomized, multicenter trial against placebo. J Affect Disord 1995; 33: 1–9

    Article  PubMed  CAS  Google Scholar 

  86. Georgotas A, Thomas L, Forsell TL, et al. Trazodone hydrochloride: a wide spectrum antidepressant with a unique pharmacological profile: a review of its neurochemical effects, pharmacology, clinical efficacy, and toxicology. Pharmacotherapy 1982; 2: 255–64

    PubMed  CAS  Google Scholar 

  87. Murphy DL, Mueller EA, Hill JL, et al. Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology 1989; 98: 275–82

    Article  PubMed  CAS  Google Scholar 

  88. Barbhaiya RH, Buch AB, Greene DS. Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan. Br J Pharmacol 1996; 42: 573–81

    CAS  Google Scholar 

  89. Nutt D. Early action of nefazodone in anxiety associated with depression. J Psychopharmacol 1996; 10Suppl. 1: 18–21

    CAS  Google Scholar 

  90. Baldwin DS, Hawley CJ, Abed RT, et al. A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate-to-severe depression. J Clin Psychiatry 1996; 57Suppl. 2: 46–52

    PubMed  CAS  Google Scholar 

  91. Robinson DS, Roberts DL, Smith JM, et al. The safety profile of nefazodone. J Clin Psychiatry 1996; 57Suppl. 2: 31–8

    PubMed  CAS  Google Scholar 

  92. van Laar MW, van Willigenburg APP, Volkerts ER. Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adults and elderly subjects. J Clin Psychopharmacol 1995; 15: 30–40

    Article  PubMed  Google Scholar 

  93. Barbhaiya RH, Buch AB, Greene DS. A study of the effect of age and gender on the pharmacokinetics of nefazodone after single and multiple doses. J Clin Psychopharmacol 1996; 16: 19–25

    Article  PubMed  CAS  Google Scholar 

  94. Feighner JP. The role of venlafaxine in rational antidepressant therapy. J Clin Psychiatry 1994; 55 (9 Suppl. A): 62–8

    PubMed  Google Scholar 

  95. Rudorfer MV, Potter WZ. Antidepressants: a comparative review of the clinical pharmacology and therapeutic use of the ‘newer’ versus the ‘older’ drugs. Drugs 1989; 37: 713–38

    Article  PubMed  CAS  Google Scholar 

  96. Rudorfer MV, Potter WZ. The role of metabolites of antidepressants in the treatment of depression. CNS Drugs 1997; 7(4): 273–312

    Article  CAS  Google Scholar 

  97. Sweet RA, Pollock BG, Kirshner M, et al. Pharmacokinetics of single- and multiple- dose bupropion in elderly patients with depression. J Clin Pharmacol 1995; 35: 876–84

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alastair J. Flint.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Flint, A.J. Choosing Appropriate Antidepressant Therapy in the Elderly. Drugs & Aging 13, 269–280 (1998). https://doi.org/10.2165/00002512-199813040-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199813040-00003

Keywords

Navigation